Giovanni Sarnelli | Università degli Studi di Napoli "Federico II" (original) (raw)

Papers by Giovanni Sarnelli

Research paper thumbnail of Effect of Dewaxed Coffee on Gastroesophageal Symptoms in Patients with GERD: A Randomized Pilot Study

Nutrients

Gastroesophageal Reflux Disease (GERD) is multifactorial pathogenesis characterized by the abnorm... more Gastroesophageal Reflux Disease (GERD) is multifactorial pathogenesis characterized by the abnormal reflux of stomach contents into the esophagus. Symptoms are worse after the ingestion of certain foods, such as coffee. Hence, a randomized pilot study conducted on 40 Italian subjects was assessed to verify the effect of standard (SC) and dewaxed coffee (DC) consumption on gastroesophageal reflux symptoms and quality of life in patients with gastrointestinal diseases. The assessment of patient diaries highlighted a significant percentage reduction of symptoms frequency when consuming DC and a significant increase in both heartburn-free and regurgitation-free days. Consequentially, patients had a significant increase of antacid-free days during the DC assumption. Moreover, the polyphenolic profile of coffee pods was ascertained through UHPLC-Q-Orbitrap HRMS analysis. Chlorogenic acids (CGAs) were the most abundant investigated compounds with a concentration level ranging between 7.316...

Research paper thumbnail of Lifestyles, Medical Therapy, and Chemoprevention

Revisiting Barrett's Esophagus, 2018

Epidemiological data indicate that Barrett’s esophagus (BE) and esophageal adenocarcinoma (EAC) h... more Epidemiological data indicate that Barrett’s esophagus (BE) and esophageal adenocarcinoma (EAC) have been increasing in incidence, particularly in developed and westernized countries. Although the pathogenesis of BE is poorly understood, evidence exists that the increasing incidence is not solely due to changes in diagnostic practice, but can most likely be attributed to temporal changes in exposure to lifestyle-related and disease-associated risk factors. This chapter will discuss risk factors for BE and will summarize possible preventive measures for development and degeneration of BE.

Research paper thumbnail of Evaluation of reflux following sleeve gastrectomy and one anastomosis gastric bypass: 1-year results from a randomized open-label controlled trial

Surgical Endoscopy, 2020

Background Recent reports have demonstrated that de novo reflux and worsening of pre-existing sym... more Background Recent reports have demonstrated that de novo reflux and worsening of pre-existing symptoms occur after SG; concerns are still expressed about the risk of symptomatic biliary reflux gastritis and oesophagitis. The aim of our study was to investigate and compare the rate of postoperative acid and non-acid reflux following Mini-/One anastomosis gastric bypass (MGB/OAGB) and laparoscopic sleeve gastrectomy (LSG). Study design A prospective randomized open-label, controlled trial registered on clinicaltrial.gov (NCT number: NCT02987673) has been carried out to evaluate esophagogastric junction exposure to reflux in the first year after MGB/OAGB and LSG using high impedance manometry, endoscopy, and a validated questionnaire. Results A total of 58 individuals were eventually enrolled in this trial and represented the per-protocol population (n = 28 MGB/OAGB, n = 30 LSG). No difference was found between the two groups in terms of demographic characteristics, PAGI-SYM score, aci...

Research paper thumbnail of Postprandial Gastrointestinal Function Differs after Acute Administration of Sourdough Compared with Brewer's Yeast Bakery Products in Healthy Adults

The Journal of nutrition, Feb 1, 2018

Europeans consume large quantities of bakery products, although these are known as one of the foo... more Europeans consume large quantities of bakery products, although these are known as one of the food categories that potentially leads to postprandial symptoms (such as fullness and bloating). The aim of this study was to evaluate the effects of sourdough baked goods on gastric emptying and gastrointestinal fermentation and symptoms in healthy people. In a double-blind, randomized crossover study, 2 sourdough croissants (SCs) or 2 brewer's yeast croissants (BCs) were served as single meals to 17 healthy adults [9 women; age range: 18-40 y; body mass index range (in kg/m2): 18-24]. Gastric volume (GV) was evaluated by magnetic resonance to calculate gastric-emptying rate in the 3-h interval after croissant ingestion. A hydrogen breath test was performed to measure hydrogen production after SC and BC ingestion. Palatability and postprandial gastrointestinal symptoms (discomfort, nausea, fullness, and bloating) over a 4-h period after the meal were evaluated. The area under the curve...

Research paper thumbnail of Pharmacokinetic drug evaluation of rifaximin for treatment of diarrhea-predominant irritable bowel syndrome

Expert opinion on drug metabolism & toxicology, Jan 13, 2018

Rifaximin is a poorly absorbable antibiotic with a broad-spectrum activity against both Gram-nega... more Rifaximin is a poorly absorbable antibiotic with a broad-spectrum activity against both Gram-negative and -positive bacteria. It is active in the small intestine due to its high bile solubility, whereas in the aqueous environment of the colon, it shows limited efficacy against highly susceptible bacteria. These unique pharmacokinetic properties limit its systemic effects and can correct gut microflora imbalances. Thus, rifaximin has become a major therapeutic agent in several gastrointestinal diseases in which an imbalance in gut microflora may play a role, including diarrhea predominant irritable bowel syndrome (IBS-D). This is an up-to-date review focusing on the efficacy of rifaximin in the treatment of IBS-D in both adult and pediatric populations. We will review the pharmacokinetic properties of rifaximin, including its absorption in health and disease, mechanisms of action, and interactions with other drugs. Given its safety profile and its negligible absorption, rifaximin is ...

Research paper thumbnail of Cortical representation of different taste modalities on the gustatory cortex: A pilot study

PloS one, 2017

Right insular cortex is involved in taste discrimination, but its functional organization is stil... more Right insular cortex is involved in taste discrimination, but its functional organization is still poorly known. In general, sensory cortices represent the spatial prevalence of relevant features for each sensory modality (visual, auditory, somatosensory) in an ordered way across the cortical space. Following this analogy, we hypothesized that primary taste cortex is organized in similar ordered way in response to six tastes with known receptorial mechanisms (sweet, bitter, sour, salt, umami, CO2). Ten normal subjects were enrolled in a pilot study. We used functional magnetic resonance imaging (fMRI), a high resolution cortical registration method, and specialized procedures of feature prevalence localization, to map fMRI responses within the right insular cortex, to water solutions of quinine hydrochloride (bitter), Acesulfamate K (sweet), sodium chloride (salt), mono potassium glutamate + inosine 5' mono phosphate (Umami), citric acid (sour) and carbonated water (CO2). During...

Research paper thumbnail of Ketogal: A Derivative Ketorolac Molecule with Minor Ulcerogenic and Renal Toxicity

Frontiers in pharmacology, 2017

Ketorolac is a powerful non-steroidal anti-inflammatory drug (NSAID), with a great analgesic acti... more Ketorolac is a powerful non-steroidal anti-inflammatory drug (NSAID), with a great analgesic activity, present on the Italian market since 1991. Despite the excellent therapeutic activity, the chronic use of ketorolac has long been limited owing to the high incidence of gastrointestinal and kidney side events. In our previous study, we demonstrated that ketorolac-galactose conjugate (ketogal), synthesized and tested in a single-dose study, was able to reduce ulcerogenicity, while preserving the high pharmacological efficacy of its parent drug. In this paper, in order to verify the suitability of this compound, for repeated administration, ex vivo experiments on naïve mice were performed. Mice were treated for 5 or 7 days with the highest doses of two drugs (ketorolac 10 mg/kg and ketogal 16.3 mg/kg), and the expression of both gastric COX-1 and PGsyn was evaluated. Results showed that oral ketorolac treatment significantly reduced both enzymes; surprisingly, oral treatment with keto...

Research paper thumbnail of Complementary and alternative treatment in functional dyspepsia

United European Gastroenterology Journal, 2017

Introduction and aim The popularity of complementary and alternative medicine (CAM) in treating f... more Introduction and aim The popularity of complementary and alternative medicine (CAM) in treating functional gastrointestinal disorders (FGIDs) has steadily increased in Western countries. We aimed at analyzing available data on CAM effectiveness in functional dyspepsia (FD) patients. Methods A bibliographical search was performed in PubMed using the following keywords: “complementary/alternative medicine,” “hypnosis,” “acupuncture” and/or “functional dyspepsia.” Results In community settings, almost 50% of patients with FGIDs used CAM therapies. Herbal remedies consist of multi-component preparations, whose mechanisms of action have not been systematically clarified. Few studies analyzed the effectiveness of acupuncture in Western countries, yielding conflicting results and possibly reflecting a population bias of this treatment. Hypnosis has been extensively used in irritable bowel syndrome, but few data support its role in treating FD. Conclusions Although some supporting well-desi...

Research paper thumbnail of Specific dyspeptic symptoms are associated with poor response to therapy in patients with gastroesophageal reflux disease

United European Gastroenterology Journal, 2017

Research paper thumbnail of Detection of colonic dysplasia in patients with ulcerative colitis using a targeted fluorescent peptide and confocal laser endomicroscopy: A pilot study

PloS one, 2017

Targeted molecular probes have been used to detect sporadic colonic dysplasia during confocal las... more Targeted molecular probes have been used to detect sporadic colonic dysplasia during confocal laser endomicroscopy (CLE) with promising results. This is a feasibility pilot study aiming to assess the potential role of CLE combined with a fluorescent-labeled peptide to stain and detect dysplasia associated with Ulcerative Colitis. A phage-derived heptapeptide with predicted high binding affinity for dysplastic tissue, was synthesized and labeled with fluorescein. Eleven lesions with suspected dysplasia at endoscopy were excised from nine patients with long-standing ulcerative colitis. Specimens were sprayed with the peptide and examined by CLE. The CLE images were then compared to the corresponding histological sections. At definitive histology, 4 lesions were diagnosed as inflammatory polyps, 6 as dysplastic lesions and one as invasive cancer. In inflammatory polyps, the fluorescence signal came from peri-cryptal spaces and crypt lumen due to passive accumulation of the peptide in t...

Research paper thumbnail of Cannabidiol restores intestinal barrier dysfunction and inhibits the apoptotic process induced by Clostridium difficile toxin A in Caco‐2 cells

United European Gastroenterology Journal, 2017

BackgroundClostridium difficile toxin A is responsible for colonic damage observed in infected pa... more BackgroundClostridium difficile toxin A is responsible for colonic damage observed in infected patients. Drugs able to restore Clostridium difficile toxin A‐induced toxicity have the potential to improve the recovery of infected patients. Cannabidiol is a non‐psychotropic component of Cannabis sativa, which has been demonstrated to protect enterocytes against chemical and/or inflammatory damage and to restore intestinal mucosa integrity.ObjectiveThe purpose of this study was to evaluate (a) the anti‐apoptotic effect and (b) the mechanisms by which cannabidiol protects mucosal integrity in Caco‐2 cells exposed to Clostridium difficile toxin A.MethodsCaco‐2 cells were exposed to Clostridium difficile toxin A (30 ng/ml), with or without cannabidiol (10−7 –10−9 M), in the presence of the specific antagonist AM251 (10−7 M). Cytotoxicity assay, transepithelial electrical resistence measurements, immunofluorescence analysis and immunoblot analysis were performed in the different experime...

Research paper thumbnail of Palmitoylethanolamide Exerts Antiproliferative Effect and Downregulates VEGF Signaling in Caco-2 Human Colon Carcinoma Cell Line Through a Selective PPAR-α-Dependent Inhibition of Akt/mTOR Pathway

Phytotherapy research : PTR, 2016

Palmitoylethanolamide (PEA) is a nutraceutical compound that has been demonstrated to improve int... more Palmitoylethanolamide (PEA) is a nutraceutical compound that has been demonstrated to improve intestinal inflammation. We aimed at evaluating its antiproliferative and antiangiogenic effects in human colon adenocarcinoma Caco-2 cell line. Caco-2 cells were treated with increasing concentrations of PEA (0.001, 0.01 and 0.1 μM) in the presence of peroxisome proliferator-activated receptor-a (PPAR-α) or PPAR-γ antagonists. Cell proliferation was evaluated by performing a MTT assay. Vascular endothelial growth factor (VEGF) release was estimated by ELISA, while the expression of VEGF receptor and the activation of the Akt/mammalian target of rapamycin (mTOR) pathway were evaluated by western blot analysis. PEA caused a significant and concentration-dependent decrease of Caco-2 cell proliferation at 48 h. PEA administration significantly reduced in a concentration-dependent manner VEGF secretion and VEGF receptor expression. Inhibition of Akt phosphorylation and a downstream decrease of ...

Research paper thumbnail of Autologous transplantation of intestine-isolated glia cells improves neuropathology and restores cognitive deficits in β amyloid-induced neurodegeneration

Scientific Reports, 2016

Alzheimer’s disease (AD) is characterized by chronic deposition of β-amyloid (Aβ) in the brain, p... more Alzheimer’s disease (AD) is characterized by chronic deposition of β-amyloid (Aβ) in the brain, progressive neurodegeneration and consequent cognitive and behavioral deficits that typify the disease. Astrocytes are pivotal in this process because they are activated in the attempt to digest Aβ which starts a neuroinflammatory response that further contributes to neurodegeneration. The intestine is a good source of astrocytes-like cells-referred to as enteric glial cells (EGCs). Here we show that the autologous transplantation of EGCs into the brain of Aβ-injected rats arrested the development of the disease after their engraftment. Transplanted EGCs showed anti-amyloidogenic activity, embanked Aβ-induced neuroinflammation and neurodegeneration and released neutrophic factors. The overall result was the amelioration of the pathological hallmarks and the cognitive and behavioral deficits typical of Aβ-associated disease. Our data indicate that autologous EGCs transplantation may provid...

Research paper thumbnail of Endoscopic treatment of esophageal achalasia

World journal of gastrointestinal endoscopy, Jan 25, 2016

Achalasia is a motility disorder of the esophagus characterized by dysphagia, regurgitation of un... more Achalasia is a motility disorder of the esophagus characterized by dysphagia, regurgitation of undigested food, chest pain, weight loss and respiratory symptoms. The most common form of achalasia is the idiopathic one. Diagnosis largely relies upon endoscopy, barium swallow study, and high resolution esophageal manometry (HRM). Barium swallow and manometry after treatment are also good predictors of success of treatment as it is the residue symptomatology. Short term improvement in the symptomatology of achalasia can be achieved with medical therapy with calcium channel blockers or endoscopic botulin toxin injection. Even though few patients can be cured with only one treatment and repeat procedure might be needed, long term relief from dysphagia can be obtained in about 90% of cases with either surgical interventions such as laparoscopic Heller myotomy or with endoscopic techniques such pneumatic dilatation or, more recently, with per-oral endoscopic myotomy. Age, sex, and manometr...

Research paper thumbnail of The HLA-DQβ1 insertion is a strong achalasia risk factor and displays a geospatial north-south gradient among Europeans

European journal of human genetics : EJHG, Aug 6, 2016

Idiopathic achalasia is a severe motility disorder of the esophagus and is characterized by a fai... more Idiopathic achalasia is a severe motility disorder of the esophagus and is characterized by a failure of the lower esophageal sphincter to relax due to a loss of neurons in the myenteric plexus. Most recently, we identified an eight-amino-acid insertion in the cytoplasmic tail of HLA-DQβ1 as strong achalasia risk factor in a sample set from Central Europe, Italy and Spain. Here, we tested whether the HLA-DQβ1 insertion also confers achalasia risk in the Polish and Swedish population. We could replicate the initial findings and the insertion shows strong achalasia association in both samples (Poland P=1.84 × 10(-04), Sweden P=7.44 × 10(-05)). Combining all five European data sets - Central Europe, Italy, Spain, Poland and Sweden - the insertion is achalasia associated with Pcombined=1.67 × 10(-35). In addition, we observe that the frequency of the insertion shows a geospatial north-south gradient. The insertion is less common in northern (around 6-7% in patients and 2% in controls fr...

Research paper thumbnail of Palmitoylethanolamide Regulates Production of Pro-Angiogenic Mediators in a Model of β Amyloid-Induced Astrogliosis In Vitro

CNS & Neurological Disorders - Drug Targets, 2015

Aβ-induced astrogliosis can worsen the eziopathogenesis of Alzheimer disease (AD) by the release ... more Aβ-induced astrogliosis can worsen the eziopathogenesis of Alzheimer disease (AD) by the release of pro-inflammatory and pro-oxidant mediators. Activated glial cells may release also pro-angiogenic molecules. The role of angiogenesis in AD is still controversial: although angiogenesis brings oxygen and nutrients to injured tissue, it may also exacerbate reactive gliosis. Moreover, by altering blood-brain barrier permeability pro-angiogenic mediators promote passage of inflammatory/immune-competent cells into the brain, thereby exacerbating gliosis. The release of pro-angiogenic factors during astrogliosis may thus be a key-step in controlling AD progression. The endogenous fatty acid amide, palmitoylethanolamide (PEA), is a pleiotropic mediator exerting anti-inflammatory, antinociceptive and anti-angiogenic effects in several in vitro and in vivo models of chronic-degenerative disease. In this study, we investigated the effects of PEA in AD angiogenesis and neuroinflammation by using conditioned medium from untreated and Aβ-treated C6 rat astroglioma cells and HUVEC human endothelial cells. PEA (10-8-10-6 M) concentration-dependently reduced expression of pro-inflammatory and pro-angiogenic markers in Aβ (1 μg/mL)-stimulated C6 cells. Moreover, culture medium from PEA-treated C6 cells reduced HUVEC cell proliferation as compared to cells treated with conditioned medium from Aβ-treated C6 cells. Immunocytochemical analysis revealed that PEA treatment inhibited nuclear levels of mitogen-activated protein kinase 1 (the main pro-angiogenic pathway) and cytoplasmic vascular endothelial growth factor in HUVEC cells receiving C6 conditioned medium. Finally, the peroxisome proliferator-activated receptor alpha inhibitor GW6471, added to Aβ-treated C6 cells blocked all PEA effects in this model, suggesting that PEA acts through a proliferator-activated receptor alpha-dependent mechanism on astroglial cells. Collectively, these data support the potential therapeutic utility of PEA in AD.

Research paper thumbnail of Pentamidine niosomes thwart S100B effects in human colon carcinoma biopsies favouring wt p53 rescue

Journal of Cellular and Molecular Medicine, 2020

This is an open access article under the terms of the Creative Commons Attribution License, which... more This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.

Research paper thumbnail of Can the enteric nervous system be an alternative entrance door in SARS-CoV2 neuroinvasion?

Brain, Behavior, and Immunity, 2020

Elsevier has created a COVID-19 resource centre with free information in English and Mandarin on ... more Elsevier has created a COVID-19 resource centre with free information in English and Mandarin on the novel coronavirus COVID-19. The COVID-19 resource centre is hosted on Elsevier Connect, the company's public news and information website. Elsevier hereby grants permission to make all its COVID-19-related research that is available on the COVID-19 resource centre-including this research content-immediately available in PubMed Central and other publicly funded repositories, such as the WHO COVID database with rights for unrestricted research re-use and analyses in any form or by any means with acknowledgement of the original source. These permissions are granted for free by Elsevier for as long as the COVID-19 resource centre remains active.

Research paper thumbnail of Rationale and evidences for treatment of symptomatic uncomplicated diverticular disease

Minerva gastroenterologica e dietologica, Jan 14, 2016

Symptomatic uncomplicated diverticular disease (SUDD) is one of the possible clinical manifestati... more Symptomatic uncomplicated diverticular disease (SUDD) is one of the possible clinical manifestations of diverticular disease. It is a common disorder characterized by chronic abdominal symptoms ranging from lower left abdominal pain to alteration of bowel habit, that significantly reduce quality of life of subject affected. The present article aims to review the current data for medical management of SUDD. We analyzed the existing literature on the factors involved in the pathogenesis of SUDD and we highlighted the possible target for treatment. Treatment for SUDD should be direct to relieve chronic symptoms and prevent diverticulitis and its complications. In particular we focused on the role of probiotics, fiber-diet, mesalazine and rifaximin on these two aspects. In this setting, we conducted a PUBMED search for guidelines, systematic reviews and meta-analyses and updated information to October 2016. Each topic was evaluated according to the best evidences available. Best results...

Research paper thumbnail of Good adherence to mediterranean diet can prevent gastrointestinal symptoms: A survey from Southern Italy

World Journal of Gastrointestinal Pharmacology and Therapeutics, 2016

To evaluate how different levels of adherence to a mediterranean diet (MD) correlate with the ons... more To evaluate how different levels of adherence to a mediterranean diet (MD) correlate with the onset of functional gastrointestinal disorders. As many as 1134 subjects (598 M and 536 F; age range 17-83 years) were prospectively investigated in relation to their dietary habits and the presence of functional gastrointestinal symptoms. Patients with relevant chronic organic disease were excluded from the study. The Mediterranean Diet Quality index for children and adolescents (KIDMED) and the Short Mediterranean Diet Questionnaire were administered. All subjects were grouped into five categories according to their ages: 17-24 years; 25-34; 35-49; 50-64; above 64. On the basis of the Rome III criteria, our population consisted of 719 (63.4%) individuals who did not meet the criteria for any functional disorder and were classified as controls (CNT), 172 (13.3%) patients meeting criteria for prevalent irritable bowel syndrome (IBS), and 243 (23.3%) meeting criteria for prevalent functional dyspepsia (FD). A significantly lower adherence score in IBS (0.57 ± 0.23, P < 0.001) and FD (0.56 ± 0.24, P < 0.05) was found compared to CNT (0.62 ± 0.21). Females with FD and IBS exhibited significantly lower adherence scores (respectively 0.58 ± 0.24, P < 0.05 and 0.56 ± 0.22, P < 0.05) whereas males were significantly lower only for FD (0.53 ± 0.25, P < 0.05). Age cluster analyses showed a significantly lower score in the 17-24 years and 25-34 year categories for FD (17-24 years: 0.44 ± 0.21, P < 0.001; 25-34 years: 0.48 ± 0.22, P < 0.05) and IBS (17-24 years: 0.45 ± 0.20, P < 0.05; 24-34 years: 0.44 ± 0.21, P < 0.001) compared to CNT (17-24 years: 0.56 ± 0.21; 25-34 years: 0.69 ± 0.20). Low adherence to MD may trigger functional gastrointestinal symptoms, mainly in younger subjects. Moreover, with increasing age, patients tend to adopt dietary regimens closer to MD.

Research paper thumbnail of Effect of Dewaxed Coffee on Gastroesophageal Symptoms in Patients with GERD: A Randomized Pilot Study

Nutrients

Gastroesophageal Reflux Disease (GERD) is multifactorial pathogenesis characterized by the abnorm... more Gastroesophageal Reflux Disease (GERD) is multifactorial pathogenesis characterized by the abnormal reflux of stomach contents into the esophagus. Symptoms are worse after the ingestion of certain foods, such as coffee. Hence, a randomized pilot study conducted on 40 Italian subjects was assessed to verify the effect of standard (SC) and dewaxed coffee (DC) consumption on gastroesophageal reflux symptoms and quality of life in patients with gastrointestinal diseases. The assessment of patient diaries highlighted a significant percentage reduction of symptoms frequency when consuming DC and a significant increase in both heartburn-free and regurgitation-free days. Consequentially, patients had a significant increase of antacid-free days during the DC assumption. Moreover, the polyphenolic profile of coffee pods was ascertained through UHPLC-Q-Orbitrap HRMS analysis. Chlorogenic acids (CGAs) were the most abundant investigated compounds with a concentration level ranging between 7.316...

Research paper thumbnail of Lifestyles, Medical Therapy, and Chemoprevention

Revisiting Barrett's Esophagus, 2018

Epidemiological data indicate that Barrett’s esophagus (BE) and esophageal adenocarcinoma (EAC) h... more Epidemiological data indicate that Barrett’s esophagus (BE) and esophageal adenocarcinoma (EAC) have been increasing in incidence, particularly in developed and westernized countries. Although the pathogenesis of BE is poorly understood, evidence exists that the increasing incidence is not solely due to changes in diagnostic practice, but can most likely be attributed to temporal changes in exposure to lifestyle-related and disease-associated risk factors. This chapter will discuss risk factors for BE and will summarize possible preventive measures for development and degeneration of BE.

Research paper thumbnail of Evaluation of reflux following sleeve gastrectomy and one anastomosis gastric bypass: 1-year results from a randomized open-label controlled trial

Surgical Endoscopy, 2020

Background Recent reports have demonstrated that de novo reflux and worsening of pre-existing sym... more Background Recent reports have demonstrated that de novo reflux and worsening of pre-existing symptoms occur after SG; concerns are still expressed about the risk of symptomatic biliary reflux gastritis and oesophagitis. The aim of our study was to investigate and compare the rate of postoperative acid and non-acid reflux following Mini-/One anastomosis gastric bypass (MGB/OAGB) and laparoscopic sleeve gastrectomy (LSG). Study design A prospective randomized open-label, controlled trial registered on clinicaltrial.gov (NCT number: NCT02987673) has been carried out to evaluate esophagogastric junction exposure to reflux in the first year after MGB/OAGB and LSG using high impedance manometry, endoscopy, and a validated questionnaire. Results A total of 58 individuals were eventually enrolled in this trial and represented the per-protocol population (n = 28 MGB/OAGB, n = 30 LSG). No difference was found between the two groups in terms of demographic characteristics, PAGI-SYM score, aci...

Research paper thumbnail of Postprandial Gastrointestinal Function Differs after Acute Administration of Sourdough Compared with Brewer's Yeast Bakery Products in Healthy Adults

The Journal of nutrition, Feb 1, 2018

Europeans consume large quantities of bakery products, although these are known as one of the foo... more Europeans consume large quantities of bakery products, although these are known as one of the food categories that potentially leads to postprandial symptoms (such as fullness and bloating). The aim of this study was to evaluate the effects of sourdough baked goods on gastric emptying and gastrointestinal fermentation and symptoms in healthy people. In a double-blind, randomized crossover study, 2 sourdough croissants (SCs) or 2 brewer's yeast croissants (BCs) were served as single meals to 17 healthy adults [9 women; age range: 18-40 y; body mass index range (in kg/m2): 18-24]. Gastric volume (GV) was evaluated by magnetic resonance to calculate gastric-emptying rate in the 3-h interval after croissant ingestion. A hydrogen breath test was performed to measure hydrogen production after SC and BC ingestion. Palatability and postprandial gastrointestinal symptoms (discomfort, nausea, fullness, and bloating) over a 4-h period after the meal were evaluated. The area under the curve...

Research paper thumbnail of Pharmacokinetic drug evaluation of rifaximin for treatment of diarrhea-predominant irritable bowel syndrome

Expert opinion on drug metabolism & toxicology, Jan 13, 2018

Rifaximin is a poorly absorbable antibiotic with a broad-spectrum activity against both Gram-nega... more Rifaximin is a poorly absorbable antibiotic with a broad-spectrum activity against both Gram-negative and -positive bacteria. It is active in the small intestine due to its high bile solubility, whereas in the aqueous environment of the colon, it shows limited efficacy against highly susceptible bacteria. These unique pharmacokinetic properties limit its systemic effects and can correct gut microflora imbalances. Thus, rifaximin has become a major therapeutic agent in several gastrointestinal diseases in which an imbalance in gut microflora may play a role, including diarrhea predominant irritable bowel syndrome (IBS-D). This is an up-to-date review focusing on the efficacy of rifaximin in the treatment of IBS-D in both adult and pediatric populations. We will review the pharmacokinetic properties of rifaximin, including its absorption in health and disease, mechanisms of action, and interactions with other drugs. Given its safety profile and its negligible absorption, rifaximin is ...

Research paper thumbnail of Cortical representation of different taste modalities on the gustatory cortex: A pilot study

PloS one, 2017

Right insular cortex is involved in taste discrimination, but its functional organization is stil... more Right insular cortex is involved in taste discrimination, but its functional organization is still poorly known. In general, sensory cortices represent the spatial prevalence of relevant features for each sensory modality (visual, auditory, somatosensory) in an ordered way across the cortical space. Following this analogy, we hypothesized that primary taste cortex is organized in similar ordered way in response to six tastes with known receptorial mechanisms (sweet, bitter, sour, salt, umami, CO2). Ten normal subjects were enrolled in a pilot study. We used functional magnetic resonance imaging (fMRI), a high resolution cortical registration method, and specialized procedures of feature prevalence localization, to map fMRI responses within the right insular cortex, to water solutions of quinine hydrochloride (bitter), Acesulfamate K (sweet), sodium chloride (salt), mono potassium glutamate + inosine 5' mono phosphate (Umami), citric acid (sour) and carbonated water (CO2). During...

Research paper thumbnail of Ketogal: A Derivative Ketorolac Molecule with Minor Ulcerogenic and Renal Toxicity

Frontiers in pharmacology, 2017

Ketorolac is a powerful non-steroidal anti-inflammatory drug (NSAID), with a great analgesic acti... more Ketorolac is a powerful non-steroidal anti-inflammatory drug (NSAID), with a great analgesic activity, present on the Italian market since 1991. Despite the excellent therapeutic activity, the chronic use of ketorolac has long been limited owing to the high incidence of gastrointestinal and kidney side events. In our previous study, we demonstrated that ketorolac-galactose conjugate (ketogal), synthesized and tested in a single-dose study, was able to reduce ulcerogenicity, while preserving the high pharmacological efficacy of its parent drug. In this paper, in order to verify the suitability of this compound, for repeated administration, ex vivo experiments on naïve mice were performed. Mice were treated for 5 or 7 days with the highest doses of two drugs (ketorolac 10 mg/kg and ketogal 16.3 mg/kg), and the expression of both gastric COX-1 and PGsyn was evaluated. Results showed that oral ketorolac treatment significantly reduced both enzymes; surprisingly, oral treatment with keto...

Research paper thumbnail of Complementary and alternative treatment in functional dyspepsia

United European Gastroenterology Journal, 2017

Introduction and aim The popularity of complementary and alternative medicine (CAM) in treating f... more Introduction and aim The popularity of complementary and alternative medicine (CAM) in treating functional gastrointestinal disorders (FGIDs) has steadily increased in Western countries. We aimed at analyzing available data on CAM effectiveness in functional dyspepsia (FD) patients. Methods A bibliographical search was performed in PubMed using the following keywords: “complementary/alternative medicine,” “hypnosis,” “acupuncture” and/or “functional dyspepsia.” Results In community settings, almost 50% of patients with FGIDs used CAM therapies. Herbal remedies consist of multi-component preparations, whose mechanisms of action have not been systematically clarified. Few studies analyzed the effectiveness of acupuncture in Western countries, yielding conflicting results and possibly reflecting a population bias of this treatment. Hypnosis has been extensively used in irritable bowel syndrome, but few data support its role in treating FD. Conclusions Although some supporting well-desi...

Research paper thumbnail of Specific dyspeptic symptoms are associated with poor response to therapy in patients with gastroesophageal reflux disease

United European Gastroenterology Journal, 2017

Research paper thumbnail of Detection of colonic dysplasia in patients with ulcerative colitis using a targeted fluorescent peptide and confocal laser endomicroscopy: A pilot study

PloS one, 2017

Targeted molecular probes have been used to detect sporadic colonic dysplasia during confocal las... more Targeted molecular probes have been used to detect sporadic colonic dysplasia during confocal laser endomicroscopy (CLE) with promising results. This is a feasibility pilot study aiming to assess the potential role of CLE combined with a fluorescent-labeled peptide to stain and detect dysplasia associated with Ulcerative Colitis. A phage-derived heptapeptide with predicted high binding affinity for dysplastic tissue, was synthesized and labeled with fluorescein. Eleven lesions with suspected dysplasia at endoscopy were excised from nine patients with long-standing ulcerative colitis. Specimens were sprayed with the peptide and examined by CLE. The CLE images were then compared to the corresponding histological sections. At definitive histology, 4 lesions were diagnosed as inflammatory polyps, 6 as dysplastic lesions and one as invasive cancer. In inflammatory polyps, the fluorescence signal came from peri-cryptal spaces and crypt lumen due to passive accumulation of the peptide in t...

Research paper thumbnail of Cannabidiol restores intestinal barrier dysfunction and inhibits the apoptotic process induced by Clostridium difficile toxin A in Caco‐2 cells

United European Gastroenterology Journal, 2017

BackgroundClostridium difficile toxin A is responsible for colonic damage observed in infected pa... more BackgroundClostridium difficile toxin A is responsible for colonic damage observed in infected patients. Drugs able to restore Clostridium difficile toxin A‐induced toxicity have the potential to improve the recovery of infected patients. Cannabidiol is a non‐psychotropic component of Cannabis sativa, which has been demonstrated to protect enterocytes against chemical and/or inflammatory damage and to restore intestinal mucosa integrity.ObjectiveThe purpose of this study was to evaluate (a) the anti‐apoptotic effect and (b) the mechanisms by which cannabidiol protects mucosal integrity in Caco‐2 cells exposed to Clostridium difficile toxin A.MethodsCaco‐2 cells were exposed to Clostridium difficile toxin A (30 ng/ml), with or without cannabidiol (10−7 –10−9 M), in the presence of the specific antagonist AM251 (10−7 M). Cytotoxicity assay, transepithelial electrical resistence measurements, immunofluorescence analysis and immunoblot analysis were performed in the different experime...

Research paper thumbnail of Palmitoylethanolamide Exerts Antiproliferative Effect and Downregulates VEGF Signaling in Caco-2 Human Colon Carcinoma Cell Line Through a Selective PPAR-α-Dependent Inhibition of Akt/mTOR Pathway

Phytotherapy research : PTR, 2016

Palmitoylethanolamide (PEA) is a nutraceutical compound that has been demonstrated to improve int... more Palmitoylethanolamide (PEA) is a nutraceutical compound that has been demonstrated to improve intestinal inflammation. We aimed at evaluating its antiproliferative and antiangiogenic effects in human colon adenocarcinoma Caco-2 cell line. Caco-2 cells were treated with increasing concentrations of PEA (0.001, 0.01 and 0.1 μM) in the presence of peroxisome proliferator-activated receptor-a (PPAR-α) or PPAR-γ antagonists. Cell proliferation was evaluated by performing a MTT assay. Vascular endothelial growth factor (VEGF) release was estimated by ELISA, while the expression of VEGF receptor and the activation of the Akt/mammalian target of rapamycin (mTOR) pathway were evaluated by western blot analysis. PEA caused a significant and concentration-dependent decrease of Caco-2 cell proliferation at 48 h. PEA administration significantly reduced in a concentration-dependent manner VEGF secretion and VEGF receptor expression. Inhibition of Akt phosphorylation and a downstream decrease of ...

Research paper thumbnail of Autologous transplantation of intestine-isolated glia cells improves neuropathology and restores cognitive deficits in β amyloid-induced neurodegeneration

Scientific Reports, 2016

Alzheimer’s disease (AD) is characterized by chronic deposition of β-amyloid (Aβ) in the brain, p... more Alzheimer’s disease (AD) is characterized by chronic deposition of β-amyloid (Aβ) in the brain, progressive neurodegeneration and consequent cognitive and behavioral deficits that typify the disease. Astrocytes are pivotal in this process because they are activated in the attempt to digest Aβ which starts a neuroinflammatory response that further contributes to neurodegeneration. The intestine is a good source of astrocytes-like cells-referred to as enteric glial cells (EGCs). Here we show that the autologous transplantation of EGCs into the brain of Aβ-injected rats arrested the development of the disease after their engraftment. Transplanted EGCs showed anti-amyloidogenic activity, embanked Aβ-induced neuroinflammation and neurodegeneration and released neutrophic factors. The overall result was the amelioration of the pathological hallmarks and the cognitive and behavioral deficits typical of Aβ-associated disease. Our data indicate that autologous EGCs transplantation may provid...

Research paper thumbnail of Endoscopic treatment of esophageal achalasia

World journal of gastrointestinal endoscopy, Jan 25, 2016

Achalasia is a motility disorder of the esophagus characterized by dysphagia, regurgitation of un... more Achalasia is a motility disorder of the esophagus characterized by dysphagia, regurgitation of undigested food, chest pain, weight loss and respiratory symptoms. The most common form of achalasia is the idiopathic one. Diagnosis largely relies upon endoscopy, barium swallow study, and high resolution esophageal manometry (HRM). Barium swallow and manometry after treatment are also good predictors of success of treatment as it is the residue symptomatology. Short term improvement in the symptomatology of achalasia can be achieved with medical therapy with calcium channel blockers or endoscopic botulin toxin injection. Even though few patients can be cured with only one treatment and repeat procedure might be needed, long term relief from dysphagia can be obtained in about 90% of cases with either surgical interventions such as laparoscopic Heller myotomy or with endoscopic techniques such pneumatic dilatation or, more recently, with per-oral endoscopic myotomy. Age, sex, and manometr...

Research paper thumbnail of The HLA-DQβ1 insertion is a strong achalasia risk factor and displays a geospatial north-south gradient among Europeans

European journal of human genetics : EJHG, Aug 6, 2016

Idiopathic achalasia is a severe motility disorder of the esophagus and is characterized by a fai... more Idiopathic achalasia is a severe motility disorder of the esophagus and is characterized by a failure of the lower esophageal sphincter to relax due to a loss of neurons in the myenteric plexus. Most recently, we identified an eight-amino-acid insertion in the cytoplasmic tail of HLA-DQβ1 as strong achalasia risk factor in a sample set from Central Europe, Italy and Spain. Here, we tested whether the HLA-DQβ1 insertion also confers achalasia risk in the Polish and Swedish population. We could replicate the initial findings and the insertion shows strong achalasia association in both samples (Poland P=1.84 × 10(-04), Sweden P=7.44 × 10(-05)). Combining all five European data sets - Central Europe, Italy, Spain, Poland and Sweden - the insertion is achalasia associated with Pcombined=1.67 × 10(-35). In addition, we observe that the frequency of the insertion shows a geospatial north-south gradient. The insertion is less common in northern (around 6-7% in patients and 2% in controls fr...

Research paper thumbnail of Palmitoylethanolamide Regulates Production of Pro-Angiogenic Mediators in a Model of β Amyloid-Induced Astrogliosis In Vitro

CNS & Neurological Disorders - Drug Targets, 2015

Aβ-induced astrogliosis can worsen the eziopathogenesis of Alzheimer disease (AD) by the release ... more Aβ-induced astrogliosis can worsen the eziopathogenesis of Alzheimer disease (AD) by the release of pro-inflammatory and pro-oxidant mediators. Activated glial cells may release also pro-angiogenic molecules. The role of angiogenesis in AD is still controversial: although angiogenesis brings oxygen and nutrients to injured tissue, it may also exacerbate reactive gliosis. Moreover, by altering blood-brain barrier permeability pro-angiogenic mediators promote passage of inflammatory/immune-competent cells into the brain, thereby exacerbating gliosis. The release of pro-angiogenic factors during astrogliosis may thus be a key-step in controlling AD progression. The endogenous fatty acid amide, palmitoylethanolamide (PEA), is a pleiotropic mediator exerting anti-inflammatory, antinociceptive and anti-angiogenic effects in several in vitro and in vivo models of chronic-degenerative disease. In this study, we investigated the effects of PEA in AD angiogenesis and neuroinflammation by using conditioned medium from untreated and Aβ-treated C6 rat astroglioma cells and HUVEC human endothelial cells. PEA (10-8-10-6 M) concentration-dependently reduced expression of pro-inflammatory and pro-angiogenic markers in Aβ (1 μg/mL)-stimulated C6 cells. Moreover, culture medium from PEA-treated C6 cells reduced HUVEC cell proliferation as compared to cells treated with conditioned medium from Aβ-treated C6 cells. Immunocytochemical analysis revealed that PEA treatment inhibited nuclear levels of mitogen-activated protein kinase 1 (the main pro-angiogenic pathway) and cytoplasmic vascular endothelial growth factor in HUVEC cells receiving C6 conditioned medium. Finally, the peroxisome proliferator-activated receptor alpha inhibitor GW6471, added to Aβ-treated C6 cells blocked all PEA effects in this model, suggesting that PEA acts through a proliferator-activated receptor alpha-dependent mechanism on astroglial cells. Collectively, these data support the potential therapeutic utility of PEA in AD.

Research paper thumbnail of Pentamidine niosomes thwart S100B effects in human colon carcinoma biopsies favouring wt p53 rescue

Journal of Cellular and Molecular Medicine, 2020

This is an open access article under the terms of the Creative Commons Attribution License, which... more This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.

Research paper thumbnail of Can the enteric nervous system be an alternative entrance door in SARS-CoV2 neuroinvasion?

Brain, Behavior, and Immunity, 2020

Elsevier has created a COVID-19 resource centre with free information in English and Mandarin on ... more Elsevier has created a COVID-19 resource centre with free information in English and Mandarin on the novel coronavirus COVID-19. The COVID-19 resource centre is hosted on Elsevier Connect, the company's public news and information website. Elsevier hereby grants permission to make all its COVID-19-related research that is available on the COVID-19 resource centre-including this research content-immediately available in PubMed Central and other publicly funded repositories, such as the WHO COVID database with rights for unrestricted research re-use and analyses in any form or by any means with acknowledgement of the original source. These permissions are granted for free by Elsevier for as long as the COVID-19 resource centre remains active.

Research paper thumbnail of Rationale and evidences for treatment of symptomatic uncomplicated diverticular disease

Minerva gastroenterologica e dietologica, Jan 14, 2016

Symptomatic uncomplicated diverticular disease (SUDD) is one of the possible clinical manifestati... more Symptomatic uncomplicated diverticular disease (SUDD) is one of the possible clinical manifestations of diverticular disease. It is a common disorder characterized by chronic abdominal symptoms ranging from lower left abdominal pain to alteration of bowel habit, that significantly reduce quality of life of subject affected. The present article aims to review the current data for medical management of SUDD. We analyzed the existing literature on the factors involved in the pathogenesis of SUDD and we highlighted the possible target for treatment. Treatment for SUDD should be direct to relieve chronic symptoms and prevent diverticulitis and its complications. In particular we focused on the role of probiotics, fiber-diet, mesalazine and rifaximin on these two aspects. In this setting, we conducted a PUBMED search for guidelines, systematic reviews and meta-analyses and updated information to October 2016. Each topic was evaluated according to the best evidences available. Best results...

Research paper thumbnail of Good adherence to mediterranean diet can prevent gastrointestinal symptoms: A survey from Southern Italy

World Journal of Gastrointestinal Pharmacology and Therapeutics, 2016

To evaluate how different levels of adherence to a mediterranean diet (MD) correlate with the ons... more To evaluate how different levels of adherence to a mediterranean diet (MD) correlate with the onset of functional gastrointestinal disorders. As many as 1134 subjects (598 M and 536 F; age range 17-83 years) were prospectively investigated in relation to their dietary habits and the presence of functional gastrointestinal symptoms. Patients with relevant chronic organic disease were excluded from the study. The Mediterranean Diet Quality index for children and adolescents (KIDMED) and the Short Mediterranean Diet Questionnaire were administered. All subjects were grouped into five categories according to their ages: 17-24 years; 25-34; 35-49; 50-64; above 64. On the basis of the Rome III criteria, our population consisted of 719 (63.4%) individuals who did not meet the criteria for any functional disorder and were classified as controls (CNT), 172 (13.3%) patients meeting criteria for prevalent irritable bowel syndrome (IBS), and 243 (23.3%) meeting criteria for prevalent functional dyspepsia (FD). A significantly lower adherence score in IBS (0.57 ± 0.23, P < 0.001) and FD (0.56 ± 0.24, P < 0.05) was found compared to CNT (0.62 ± 0.21). Females with FD and IBS exhibited significantly lower adherence scores (respectively 0.58 ± 0.24, P < 0.05 and 0.56 ± 0.22, P < 0.05) whereas males were significantly lower only for FD (0.53 ± 0.25, P < 0.05). Age cluster analyses showed a significantly lower score in the 17-24 years and 25-34 year categories for FD (17-24 years: 0.44 ± 0.21, P < 0.001; 25-34 years: 0.48 ± 0.22, P < 0.05) and IBS (17-24 years: 0.45 ± 0.20, P < 0.05; 24-34 years: 0.44 ± 0.21, P < 0.001) compared to CNT (17-24 years: 0.56 ± 0.21; 25-34 years: 0.69 ± 0.20). Low adherence to MD may trigger functional gastrointestinal symptoms, mainly in younger subjects. Moreover, with increasing age, patients tend to adopt dietary regimens closer to MD.